Intercellular communication via gap junctions has been hypothesized to play an important role in gonad development and germ cell differentiation. Gap junctions between germ line and somatic cells are widely conserved features from worms, insects, to humans. Disruptions in gap junctional intercellular communication (GJIC) may underlie certain reproductive diseases in humans, such as gonadal failure, azoospermia, and ovulatory dysfunction. However, the role of gap junctions in mammalian gonad development and gametogenesis has been difficult to investigate due to the possible redundancy among the 15 connexin genes identified in mammals and due to the essential role of gap junctions in other organs. I have discovered a Drosophila melanogaster gene, zero population growth (zpg), which encodes a germ line specific gap junction protein (innexin) and is required for germ cell differentiation in both sexes. Subcellular localization of the zpg protein suggests a critical role for gap junctional communication between germ line and somatic cells in Drosophila. Preliminary observations also suggest that zpg function is required during gonad formation. In this pilot project, I propose to use the power of Drosophila system to explore the role of gap junctional communication between germ line and somatic cells during gonad formation and germ cell differentiation. Then, using insights gained from these studies, I propose to draw functional parallels between invertebrate and vertebrate system by a pilot study analysis gap junctional communication in gonad formation and early germ cell differentiation in human and murine fetal gonads. These pilot studies are likely to provide insights into mechanisms of the pathogenesis of gonadal dysgenesis and failure. Though beyond the scope of this proposal, the long term goal is to determine if GJIC dysfunction underlie human reproductive diseases.